Design of a multivalent bifunctional chelator for diagnostic ⁶⁴Cu PET imaging in Alzheimer's disease

Herein, we report a ⁶⁴Cu positron emission tomography (PET) imaging agent that shows appreciable in vivo brain uptake and exhibits high specific affinity for beta-amyloid (Aβ) aggregates, leading to the successful PET imaging of amyloid plaques in the brains of 5xFAD mice versus those of wild-type mice. The employed approach uses a bifunctional chelator with two Aβ-interacting fragments that dramatically improves the Aβ-binding affinity and lipophilicity for favorable blood-brain barrier penetration, while the use of optimized-length spacers between the Cuchelating group and the Aβ-interacting fragments further improves the in vivo Aβ-binding specificity and brain uptake of the corresponding ⁶⁴Cu PET imaging agent.